Bromodomain Assay Services

Creative Biolabs provides bromodomain assay services to assist you in swiftly, very reproducibly, and highly sensitively identifying your compounds. Creative Biolabs is one reliable resource that can assist you in accelerating your study procedure.

While the discipline of chemical epigenetics aims to manipulate epigenetic processes using chemical methods in order to better understand biology or treat disease, the science of epigenetics describes the role of chromatin and chromatin-associated proteins. The academic and pharmaceutical communities have shown a great deal of interest in the development of highly selective bromodomain probes and drugs since the first submicromolar inhibitors of a bromodomain were revealed for the bromodomains and extraterminal (BET) family. It was previously believed that a bromodomain had 77 residues and two helices, αA and αB. These helices were also found to include seven conserved residues: two asparagines, a phenylalanine, an isoleucine, and three tyrosines. The conserved phenylalanine was a component of the bromodomain motif that would subsequently be referred to as the "WPF shelf." It would also be demonstrated later that one of the conserved tyrosine and asparagine residues is necessary for the chemical recognition of the N-ε-acetyl of acetylated lysine by bromodomains.

Fig.1 The bromodomain binding pocket.¹

Targets of Bromodomain Assay Services

Eight protein families including bromodomains were formed from 61 distinct bromodomains derived from 46 distinct human proteins. A unique structural pattern identified as the β-hairpin insert has been discovered in the class VIII bromodomain family. These families of bromodomains reflect the state of the field today. The targets of bromodomain assay services provided by Creative Biolabs are below:

Case Studies of Small-Molecule Bromodomain Inhibitor Discovery

• CREBBP

The large coactivator proteins known as CREB-binding proteins (CREBBP) have the capacity to bind transcriptional activators through protein-protein interaction modules, histone acetyltransferase activity, and histone binding via their bromodomain. Genetic knockouts of this protein have been demonstrated to result in embryonic mortality, demonstrating its vital role in development. Researchers created a targeted library of N-acetyl amine-linked aromatic ring-based acetylated lysine mimics. A compound was discovered by chemical shift perturbation-based hit deconvolution, computational docking, and an NMR solution structure. Apart from inhibiting acetylated p53 interactions in vitro, a tryptophan intrinsic fluorescence test was used to obtain a Kd of 19 μM.

• BRDs

The simultaneous announcement of the first submicromolar BET bromodomain inhibitors (BRD2, 3, 4, and T) marked a turning point in the discovery of bromodomain inhibitors. Since then, the groundwork has been laid for verifying the therapeutic potential of blocking bromodomain function in human clinical trials, thanks to these seminal reports that produced priceless molecular probes for the BET bromodomains.

Creative Biolabs offers bromodomain assay services to identify drugs that contain proteins that contain bromodomains. Researchers have been able to get additional insight into the function that bromodomain proteins play in both the development of disease and normal cellular activity. Please contact us for more information.

Reference

1. Boyson, Samuel P., et al. "Functional roles of bromodomain proteins in cancer." Cancers 13.14 (2021): 3606.